Artificial intelligence and pain medicine education: Benefits and pitfalls for the medical trainee.

Objectives: Artificial intelligence (AI) represents an exciting and evolving technology that is increasingly being utilized across pain medicine. Large language models (LLMs) are one type of AI that has become particularly popular. Currently, there is a paucity of literature analyzing the impact that AI may have on trainee education.

Multifidus atrophy and/or dysfunction following lumbar radiofrequency ablation: A systematic review.

Background: Lumbar medial branch nerve radiofrequency ablation (LRFA) is an interventional procedure used to treat chronic lumbar facet joint pain. Because the medial branch nerves also innervate the multifidus muscle, it has been proposed that LRFA may pose a risk of multifidus atrophy and/or dysfunction. However, the quality and level of evidence to answer this clinical question have not been established.

The systems-based practice competency: an innovative model to achieving class-wide proficiency in a pain medicine fellowship.

One of the ACGME's six core competencies, systems-based practice (SBP), is difficult to interpret and developing proficiency over a one-year fellowship poses a challenge. Given the implications that successful SBP can have on pain medicine, it is especially important for fellows to focus on this competency during their training. Here, we propose a way to implement effective SBP into a pain medicine fellowship and the impact it may have within the larger health care system.

A scoping review of methods used in musculoskeletal soft tissue and nerve shear wave elastography studies.

This scoping review of shear wave elastography (SWE) articles in musculoskeletal soft tissue and nerve research demonstrates methodological heterogeneity resulting from a lack of standardized data collection and reporting requirements. Seven literature databases were searched for original articles published in English from 2004-2020 that examine human skeletal muscles, tendons, and nerves in vivo. Although 5,868 records were initially identified, only 375 reports met inclusion criteria.

Surface Laplacian of interfacial thermochemical potential: its role in solid-liquid pattern formation.

Steady-state solid-liquid interfaces allow both analytic description as sharp-interface profiles, and numerical simulation via phase-field modeling as stationary diffuse-interface microstructures. Profiles for sharp interfaces reveal their exact shapes and allow identification of the thermodynamic origin of all interfacial capillary fields, including distributions of curvature, thermochemical potential, gradients, fluxes, and surface Laplacians. By contrast, simulated diffuse interface images allow thermodynamic evolution and measurement of interfacial temperatures and fluxes.

Celecoxib for Management of Refractory Back Pain Secondary to Vertebral Osteomyelitis: A Case Report.

Back pain is the most common symptom of vertebral osteomyelitis and can be difficult to manage. Pain may persist despite appropriate antibiotic medications and may be refractory to common analgesic treatments. We present a case of a 53-year-old man with acute onset severe low back pain.

Growth competition during columnar solidification of seaweed microstructures : Insights from 3-D phase-field simulations.

The mechanisms by which interfacial instabilities instigate the growth of solidification patterns is a topic of longstanding interest. In columnar solidification of metallic melts, where the solid-liquid interfacial energy is anisotropic, evolving dendritic patterns compete depending on their relative misorientation. By contrast, organic "plastic crystals", such as alloys based on succinonitrile, where the anisotropy in their solid-liquid interfacial energy is extremely weak, solidify forming seaweed patterns that typically exhibit little, if any, growth competition.

Early effects of roflumilast on insulin sensitivity in adults with prediabetes and overweight/obesity involve age-associated fat mass loss - results of an exploratory study.

Purpose: Roflumilast (Daliresp, Daxas) is a FDA-approved phosphodiesterase 4 (PDE4) inhibitor for the treatment of moderate-to-severe chronic obstructive pulmonary disease. In mice and in limited human studies, this oral medication can cause weight loss and improve insulin sensitivity. We set out to determine the mechanism of its effect on insulin sensitivity.

Non-Invasive Buccal Swab Gene Testing for Skin Cancer Risk.

Background: Studies have identified numerous genetic polymorphisms associated with increased risk of melanoma and non-melanoma skin cancer (NMSC). In this pilot study, we aimed to examine whether previously identified melanoma and non-melanoma associated single nucleotide polymorphisms (SNPs) which were found to be associated with cutaneous malignancy were also present in a relatively heterogeneous population with a history of skin cancer versus an age and environmental matched controls. The undertaking of this project serves to further the current understanding of the genetic profile for those at higher risk for developing skin cancer.

A review of clinical trials: mesenchymal stem cell transplant therapy in type 1 and type 2 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are widely prevalent metabolic diseases with differing pathologies. T1DM manifests due to autoimmune destruction of the pancreatic beta cells, resulting in a diminished secretion of insulin. T2DM originates from a state of insulin resistance, resulting in hyperglycemia and reduction in beta cell mass.

Assessing the predictive accuracy of oral glucose effectiveness index using a calibration model.

Purpose: Current reference methods for measuring glucose effectiveness (GE) are the somatostatin pancreatic glucose clamp and minimal model analysis of frequently sampled intravenous glucose tolerance test (FSIVGTT), both of which are laborious and not feasible in large epidemiological studies. Consequently, surrogate indices derived from an oral glucose tolerance test (OGTT) to measure GE (oGE) have been proposed and used in many studies. However, the predictive accuracy of these surrogates has not been formally validated.

Induced Pluripotent Stem Cells: The Most Versatile Source for Stem Cell Therapy.

Cell therapy has existed since the first bone marrow transplant in the 1950s involving identical twins. The blood-forming stem cells were used to restore healthy blood cells for the twin with leukemia. It was not until 1968 that genetic matching (known as human leukocyte antigen matching) was known to be important, and not until 1973 that bone marrow transplants were performed from non-twin-related and nonrelated donors.

Assay Guidance Manual: Quantitative Biology and Pharmacology in Preclinical Drug Discovery.

The Assay Guidance Manual (AGM) is an eBook of best practices for the design, development, and implementation of robust assays for early drug discovery. Initiated by pharmaceutical company scientists, the manual provides guidance for designing a "testing funnel" of assays to identify genuine hits using high-throughput screening (HTS) and advancing them through preclinical development. Combined with a workshop/tutorial component, the overall goal of the AGM is to provide a valuable resource for training translational scientists.

Optimization of a series of heterocycles as survival motor neuron gene transcription enhancers.

Spinal muscular atrophy (SMA) is a neurodegenerative disorder that results from mutations in the SMN1 gene, leading to survival motor neuron (SMN) protein deficiency. One therapeutic strategy for SMA is to identify compounds that enhance the expression of the SMN2 gene, which normally only is a minor contributor to functional SMN protein production, but which is unaffected in SMA. A recent high-throughput screening campaign identified a 3,4-dihydro-4-phenyl-2(1H)-quinolinone derivative (2) that increases the expression of SMN2 by 2-fold with an EC = 8.

β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson's disease.

Copy number mutations implicate excess production of α-synuclein as a possibly causative factor in Parkinson's disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene (). β2AR ligands modulate transcription through histone 3 lysine 27 acetylation of its promoter and enhancers.

Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. We previously developed a high-throughput assay that employs an SMN2-luciferase reporter allowing identification of compounds that act transcriptionally, enhance exon recognition, or stabilize the SMN protein. We describe optimization and characterization of an analog suitable for in vivo testing.

Plasma serpinB1 is related to insulin sensitivity but not pancreatic -Cell function in non-diabetic adults.

Pancreatic -cell dysfunction because of reduced -cell mass and function is a primary determinant in the progression of diabetes. Increase in -cell mass and compensatory hyperinsulinaemia is frequently associated with insulin-resistant states. Although the humoral factors mediating this compensatory response are unknown, serpinB1, a protease inhibitor, has recently been proposed to be one such factor.

Identification of Anti-prion Compounds using a Novel Cellular Assay.

Prion diseases are devastating neurodegenerative disorders with no known cure. One strategy for developing therapies for these diseases is to identify compounds that block conversion of the cellular form of the prion protein (PrP) into the infectious isoform (PrP). Most previous efforts to discover such molecules by high-throughput screening methods have utilized, as a read-out, a single kind of cellular assay system: neuroblastoma cells that are persistently infected with scrapie prions.

Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation.

Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC.

Tackling reproducibility in academic preclinical drug discovery.

The reproducibility of biomedical research on novel drug targets has become suspect. Here, we highlight how drug discovery centres embedded in academic institutions, but with a translational imperative, can help address this reproducibility crisis.

Development of a Fluorescent Quenching Based High Throughput Assay to Screen for Calcineurin Inhibitors.

Currently there is no effective treatment available for major neurodegenerative disorders associated to protein misfolding, including Alzheimer's and Parkinson's disease. One of most promising therapeutic approaches under development focuses on inhibiting the misfolding and aggregation pathway. However, it is likely that by the time clinical symptoms appear, there is a large accumulation of misfolded aggregates and a very substantial damage to the brain.